Bottom Line:
Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively.Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA.The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine.

Purpose: The effect of clinical L-3,4-dihydroxyphenylalanine (L-DOPA) doses on the binding of [121I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (121[I]FP-CIT) to the rat dopamine transporter (DAT) was investigated using small animal single-photon emission computed tomography.

Materials and methods: DAT binding was measured at baseline, after challenge with the aromatic L-amino acid decarboxylase inhibitor benserazide, and after challenge with either 5 or 10 mg/kg L-DOPA plus benserazide. For baseline and challenges, striatal equilibrium ratios (V3'') were computed as an estimation of the binding potential. Moreover, striatal V3'' values were correlated with parameters of motor and exploratory behavior.

Conclusion: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively. Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA. The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine. Moreover, there is preliminary evidence of an association between striatal DAT and motor and exploratory parameters.

Figure 2: (a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.

Figure 2: (a) Coronal [123I]FP-CIT images of the same rat head at baseline, after pretreatment with 5 mg/kg l-DOPA/benserazide, and after treatment with 10 mg/kg benserazide. The reduction in striatal DAT binding after l-DOPA is clearly visible. All images show V3′′ values; it is understood that the calculation of V3′′ is only valid for regions of specific radioligand binding such as the rat striatum. Calculations were performed using MATLAB (version 4.2c or version 6; The MathWorks Inc., Novi, Michigan, USA). (b) Striatal equilibrium ratios (V3′′) at baseline, after 5 mg/kg l-DOPA/benserazide, and after 10 mg/kg benserazide. Rendered are means and SEM. The circles represent the individual animals. DAT, dopamine transporter; [123I]FP-CIT, [123I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; l-DOPA, l-3,4-dihydroxyphenylalanine.

Bottom Line:
Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively.Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA.The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine.

Purpose: The effect of clinical L-3,4-dihydroxyphenylalanine (L-DOPA) doses on the binding of [121I]N-Ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (121[I]FP-CIT) to the rat dopamine transporter (DAT) was investigated using small animal single-photon emission computed tomography.

Materials and methods: DAT binding was measured at baseline, after challenge with the aromatic L-amino acid decarboxylase inhibitor benserazide, and after challenge with either 5 or 10 mg/kg L-DOPA plus benserazide. For baseline and challenges, striatal equilibrium ratios (V3'') were computed as an estimation of the binding potential. Moreover, striatal V3'' values were correlated with parameters of motor and exploratory behavior.

Conclusion: Challenge with 5 and 10 mg/kg L-DOPA/benserazide led to mean reductions in DAT binding by 34 and 20%, respectively. Results indicate a biphasic response with a higher effect on DAT after the lower dose of L-DOPA. The reduction in DAT binding may be interpreted in terms of competition between [123I]FP-CIT and endogenous dopamine. Moreover, there is preliminary evidence of an association between striatal DAT and motor and exploratory parameters.